Relationship between sex hormones, sex hormone bindingglobulin (SHBG) and peripheral arterial disease in older persons

Lower extremity peripheral arterial disease (PAD) is widely accepted as an indicator of generalized atherosclerosis (1). Men and women with PAD have faster functional decline and higher mortality risk compared with those without (2). In older population the prevalence of PAD is similar to or even slightly higher in women as compared with men. Moreover, women with PAD have greater mobility loss than men (3). These data suggest that PAD might be affected by sex hormones and Sex Hormone Binding Globulin (SHBG) levels. This hypothesis is supported by the evidence of metabolic actions of sex hormones and SHBG. We have previously demonstrated that low SHBG is an independent risk factor of metabolic syndrome in both sexes (4,5), whereas low testosterone and high estradiol levels are risk factors of metabolic syndrome in men (6). It is reasonable to hypothesize a similar relationship between sex hormones and PAD, but data at this regard are scant (7,8). Aim of the Study: Therefore, the aim of our study is to test the relationship between testosterone (T), estradiol (E2), SHBG and lower extremity PAD and to identify potential differences in two sexes. Methods: We selected 921 men and women aged C65 (65-102 yr) from the InCHIANTI study. T was measured by RIA (Inter- and intraassay CVs were 9.6 and 9.1%, MDC 0.08 nmol/l). SHBG was measured with IRMA (MCD 3.00 nmol/l, Inter- intra-CVs were\3.7 and 11.5). E2 was measured with ultrasensitive RIA (MCD 2.2 pg/ml and intra- inter-assay CV 8% and 10%). PAD was defined by an ABI\0.90. Means (±DS) were compared using t-test and percentages using Chi-square. Factors correlated with PAD were identified using age-adjusted partial correlation coefficient and Spearman partial rank-order correlation coefficients. Logistic regression models were used to identify independent factors of PAD : in MODEL 1 the analysis was adjusted only for age; MODEL 2 included also BMI, interleukin-6, physical activity, smoking, hypertension, chronic heart failure. MODEL 3 included covariates of Model 2, and T, SHBG, E2. Results: Mean Age (± SD) al baseline was 74.2 ± 6.5 yrs in men and 5.6 ± 7.0 in women. 62 (41 men, 21 women) had ABI\0.90 and 859 ABI[0.90. Men with ABI\0.90 had SHBG mean values of 96.9 (± 56.1), significantly lower than those with ABI[0.90 (109.3 ± 54.4) (p = 0.03); no significant trend was found in women (p = 0.22). An inverse and significant relationship was found between SHBG and PAD only in men, in Models 1 and 2 (p = 0.004and p = 0.028, respectively), but not in Model 3 (p = 0.07). In women we found a positive and significant relationship between testosterone and PAD in Models 1 and 2 (OR 5.44, CI 1.13-26.06 and OR 1.64, CI 1.01-2.67, respectively) association that was significant also in Model 3 (p = 0.01). No significant association was found between testosterone and PAD in men (OR 1.23, CI 0.95-1.58), and between E2 and PAD in both sexes. Conclusions: Peripheral arterial disease is associated with low SHBG levels in older men, and with high total testosterone levels in women. Further longitudinal studies are needed to verify the potential role of SHBG and testosterone in PAD. References 1. Lee AJ, et al. Circulation 2004 2. McDermott MM, et al. J Am Coll Cardiol 2011 3. McDermott MM, et al. J Am Coll Cardiol 2011 4. Maggio M, et al. Am J Physiol Endocrinol Met 2007 5. Maggio M, et al. J Am Geriatr Soc 2006 6. Maggio M, et al. J Androl 2010 7. Price JF, et al. Steroids 1997 8. Tivesten A ° , et al. J Am Coll Cardiol 2007